Facile fabrication of multi-pocket nanoparticles with stepwise size transition for promoting deep penetration and tumor targeting
Abstract Background Nanocarriers-derived antitumor therapeutics are often associated with issues of limited tumor penetration and dissatisfactory antitumor efficacies. Some multistage delivery systems have been constructed to address these issues, but they are often accompanied with complicated manu...
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| Format: | Article |
| Language: | English |
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BMC
2021-04-01
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| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12951-021-00854-z |
| _version_ | 1817994617988055040 |
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| author | Xingyu Hou Dan Zhong Yunkun Li Hongli Mao Jun Yang Hu Zhang Kui Luo Qiyong Gong Zhongwei Gu |
| author_facet | Xingyu Hou Dan Zhong Yunkun Li Hongli Mao Jun Yang Hu Zhang Kui Luo Qiyong Gong Zhongwei Gu |
| author_sort | Xingyu Hou |
| collection | DOAJ |
| description | Abstract Background Nanocarriers-derived antitumor therapeutics are often associated with issues of limited tumor penetration and dissatisfactory antitumor efficacies. Some multistage delivery systems have been constructed to address these issues, but they are often accompanied with complicated manufacture processes and undesirable biocompatibility, which hinder their further application in clinical practices. Herein, a novel dual-responsive multi-pocket nanoparticle was conveniently constructed through self-assembly and cross-linking of amphiphilic methoxypolyethylene glycol-lipoic acid (mPEG-LA) conjugates to enhance tumor penetration and antitumor efficacy. Results The multi-pocket nanoparticles (MPNs) had a relatively large size of ~ 170 nm at physiological pH which results in prolonged blood circulation and enhanced accumulation at the tumor site. But once extravasated into acidic tumor interstices, the increased solubility of PEG led to breakage of the supramolecular nanostructure and dissolution of MPNs to small-sized (< 20 nm) nanoparticles, promoting deep penetration and distribution in tumor tissues. Furthermore, MPNs exhibited not only an excellent stable nanostructure for antitumor doxorubicin (DOX) loading, but rapid dissociation of the nanostructure under an intracellular reductive environment. With the capacity of long blood circulation, deep tumor penetration and fast intracellular drug release, the DOX-loaded multi-pocket nanoparticles demonstrated superior antitumor activities against large 4T1 tumor (~ 250 mm3) bearing mice with reduced side effect. Conclusions Our facile fabrication of multi-pocket nanoparticles provided a promising way in improving solid tumor penetration and achieving a great therapeutic efficacy. Graphic Abstract |
| first_indexed | 2024-04-14T01:55:25Z |
| format | Article |
| id | doaj.art-7f06cd85049d41e18671336d03cff660 |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-04-14T01:55:25Z |
| publishDate | 2021-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-7f06cd85049d41e18671336d03cff6602022-12-22T02:19:07ZengBMCJournal of Nanobiotechnology1477-31552021-04-0119111310.1186/s12951-021-00854-zFacile fabrication of multi-pocket nanoparticles with stepwise size transition for promoting deep penetration and tumor targetingXingyu Hou0Dan Zhong1Yunkun Li2Hongli Mao3Jun Yang4Hu Zhang5Kui Luo6Qiyong Gong7Zhongwei Gu8Huaxi MR Research Center (HMRRC), Department of Radiology, Functional and Molecular Imaging Key Laboratory of Sichuan Province, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityHuaxi MR Research Center (HMRRC), Department of Radiology, Functional and Molecular Imaging Key Laboratory of Sichuan Province, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityHuaxi MR Research Center (HMRRC), Department of Radiology, Functional and Molecular Imaging Key Laboratory of Sichuan Province, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityResearch Institute for Biomaterials, Tech Institute for Advanced Materials, College of Materials Science and Engineering, NJTech-BARTY Joint Research Center for Innovative Medical Technology, Nanjing Tech UniversityThe Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Science, Nankai UniversityAmgen Bioprocessing Centre, Keck Graduate InstituteHuaxi MR Research Center (HMRRC), Department of Radiology, Functional and Molecular Imaging Key Laboratory of Sichuan Province, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityHuaxi MR Research Center (HMRRC), Department of Radiology, Functional and Molecular Imaging Key Laboratory of Sichuan Province, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityHuaxi MR Research Center (HMRRC), Department of Radiology, Functional and Molecular Imaging Key Laboratory of Sichuan Province, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityAbstract Background Nanocarriers-derived antitumor therapeutics are often associated with issues of limited tumor penetration and dissatisfactory antitumor efficacies. Some multistage delivery systems have been constructed to address these issues, but they are often accompanied with complicated manufacture processes and undesirable biocompatibility, which hinder their further application in clinical practices. Herein, a novel dual-responsive multi-pocket nanoparticle was conveniently constructed through self-assembly and cross-linking of amphiphilic methoxypolyethylene glycol-lipoic acid (mPEG-LA) conjugates to enhance tumor penetration and antitumor efficacy. Results The multi-pocket nanoparticles (MPNs) had a relatively large size of ~ 170 nm at physiological pH which results in prolonged blood circulation and enhanced accumulation at the tumor site. But once extravasated into acidic tumor interstices, the increased solubility of PEG led to breakage of the supramolecular nanostructure and dissolution of MPNs to small-sized (< 20 nm) nanoparticles, promoting deep penetration and distribution in tumor tissues. Furthermore, MPNs exhibited not only an excellent stable nanostructure for antitumor doxorubicin (DOX) loading, but rapid dissociation of the nanostructure under an intracellular reductive environment. With the capacity of long blood circulation, deep tumor penetration and fast intracellular drug release, the DOX-loaded multi-pocket nanoparticles demonstrated superior antitumor activities against large 4T1 tumor (~ 250 mm3) bearing mice with reduced side effect. Conclusions Our facile fabrication of multi-pocket nanoparticles provided a promising way in improving solid tumor penetration and achieving a great therapeutic efficacy. Graphic Abstracthttps://doi.org/10.1186/s12951-021-00854-zDrug deliveryParticle sizeTumor penetrationDisulfide cross-linkingFacile preparation |
| spellingShingle | Xingyu Hou Dan Zhong Yunkun Li Hongli Mao Jun Yang Hu Zhang Kui Luo Qiyong Gong Zhongwei Gu Facile fabrication of multi-pocket nanoparticles with stepwise size transition for promoting deep penetration and tumor targeting Journal of Nanobiotechnology Drug delivery Particle size Tumor penetration Disulfide cross-linking Facile preparation |
| title | Facile fabrication of multi-pocket nanoparticles with stepwise size transition for promoting deep penetration and tumor targeting |
| title_full | Facile fabrication of multi-pocket nanoparticles with stepwise size transition for promoting deep penetration and tumor targeting |
| title_fullStr | Facile fabrication of multi-pocket nanoparticles with stepwise size transition for promoting deep penetration and tumor targeting |
| title_full_unstemmed | Facile fabrication of multi-pocket nanoparticles with stepwise size transition for promoting deep penetration and tumor targeting |
| title_short | Facile fabrication of multi-pocket nanoparticles with stepwise size transition for promoting deep penetration and tumor targeting |
| title_sort | facile fabrication of multi pocket nanoparticles with stepwise size transition for promoting deep penetration and tumor targeting |
| topic | Drug delivery Particle size Tumor penetration Disulfide cross-linking Facile preparation |
| url | https://doi.org/10.1186/s12951-021-00854-z |
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